Arends N J T, Boonstra V H, Mulder P G H, Odink R J H, Stokvis-Brantsma W H, Rongen-Westerlaken C, Mulder J C, Delemarre-Van de Waal H, Reeser H M, Jansen M, Waelkens J J J, Hokken-Koelega A C S
Department of Pediatrics, Division of Endocrinology, Erasmus MC/Sophia Children's Hospital, Rotterdam, the Netherlands.
Clin Endocrinol (Oxf). 2003 Dec;59(6):779-87. doi: 10.1046/j.1365-2265.2003.01905.x.
To investigate in a group of short children born small for gestational age (SGA), the effects of 3 years of GH treatment vs. no treatment on bone age (BA), height and bone mineral density (BMD). Also, to evaluate the influence of the severity of growth retardation at start and the GH dose on the gain in height.
The study design was an open-labelled, controlled multicentre GH study for 3 years. Non-GH-deficient (GHD) children (n = 87) were randomized to either a GH group (n = 61) or an untreated control group (n = 26). In addition, 12 SGA children had GHD (GHD group) and were treated in parallel. Both the GH and the GHD group were treated with a GH dose of 33 microg/kg/day. BMD was evaluated using dual energy X-ray absorptiometry (DEXA). In addition, data of our first GH trial in which short SGA children were treated with a GH dose of 66 microg/kg/day (n = 24) were used for comparison of height gain.
In contrast to the control group, the GH group showed a significant increase in height (P < 0.001), as did the parallel GHD group. Bone maturation [delta bone age (BA)/delta calendar age (CA)] increased significantly during the first 2 years of GH treatment but slowed-down thereafter. The 3-year deltaBA/deltaCA ratio correlated significantly with the gain in height (r = 0.6, P < 0.001). At start, mean BMD SDS and mean BMAD SDS were significantly lower than zero. During GH treatment both increased impressively (P < 0.001). The gain in height of children with severe short stature at start (< or = -3.00 SDS), did not differ between those receiving either a GH dose of 33 or 66 microg/kg/day.
Three years of GH treatment in short children born SGA results in a normalization of height during childhood. Also, bone maturation increased proportionately to the height gain. At start, mean values of BMD and BMAD were significantly reduced but normalized during GH treatment. We did not find an indication to treat very short SGA children (H SDS < or = -3.00) with a higher GH dose. We rather suggest to start GH treatment at an early age in order to achieve a normal height before puberty starts.
在一组小于胎龄儿（SGA）出生的矮小儿童中，研究3年生长激素（GH）治疗与未治疗对骨龄（BA）、身高和骨密度（BMD）的影响。此外，评估起始时生长迟缓的严重程度和GH剂量对身高增长的影响。
本研究设计为一项为期3年的开放标签、对照多中心GH研究。非生长激素缺乏（GHD）儿童（n = 87）被随机分为GH组（n = 61）或未治疗对照组（n = 26）。此外，12名SGA儿童患有GHD（GHD组）并接受平行治疗。GH组和GHD组均接受33μg/kg/天的GH剂量治疗。使用双能X线吸收法（DEXA）评估BMD。此外，我们首次对矮小SGA儿童使用66μg/kg/天的GH剂量进行治疗的试验数据（n = 24）用于比较身高增长情况。
与对照组相比，GH组身高显著增加（P < 0.001），平行的GHD组也是如此。在GH治疗的前2年骨成熟度[骨龄变化（BA）/日历年龄变化（CA）]显著增加，但此后减缓。3年的BA/CA变化率与身高增长显著相关（r = 0.6，P < 0.001）。起始时，平均BMD SDS和平均骨小梁面积密度（BMAD）SDS显著低于零。在GH治疗期间两者均显著增加（P < 0.001）。起始时严重身材矮小（≤ -3.00 SDS）的儿童，接受33或66μg/kg/天GH剂量治疗的身高增长无差异。
对SGA出生的矮小儿童进行3年GH治疗可使儿童期身高正常化。此外，骨成熟度与身高增长成比例增加。起始时，BMD和BMAD的平均值显著降低，但在GH治疗期间恢复正常。我们未发现有迹象表明对非常矮小的SGA儿童（身高SDS ≤ -3.00）使用更高剂量的GH进行治疗。我们更建议在早期开始GH治疗，以便在青春期开始前达到正常身高。
